5-Bromocinnoline - ≥95% , CAS No.1823964-40-4

CAS: 1823964-40-4 Cat. No.: B944754 분자식: C₈H₅BrN₂ 분자량: 209.040 EC 번호: 997-337-7

등급 & 순도 ≥95%

Storage

Room temperature

사양

사양 및 순도

≥95%

보관 조건

Room temperature

순수함

≥95%

이름과 식별자

정식 스마일

C1=CC2=C(C=CN=N2)C(=C1)Br

IUPAC Name

5-bromocinnoline

InChIKey

RFPGSUNKMXQPKV-UHFFFAOYSA-N

INCHI

1S/C8H5BrN2/c9-7-2-1-3-8-6(7)4-5-10-11-8/h1-5H

분자량

209.040

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • 분류 Diazanaphthalenes
      • Subclass Benzodiazines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• 분류: Diazanaphthalenes
• Subclass: Benzodiazines
• Intermediate Tree Nodes: Not available
• Direct Parent: Cinnolines
• Alternative Parents: Pyridazines and derivatives Benzenoids Aryl bromides Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Cinnoline - Benzenoid - Pyridazine - Aryl halide - Aryl bromide - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Organobromide - Organohalogen compound - Aromatic heteropolycyclic compound
• 설명: This compound belongs to the class of organic compounds known as cinnolines. These are organic aromatic compounds containing a benzene fused to a pyridazine ring.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

화학 및 물리적 특성

• 분자량: 209.040 g/mol
• XLogP3: 1.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 207.964 Da
• Monoisotopic Mass: 207.964 Da
• Topological Polar Surface Area: 25.800 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 140.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Not applicable. There are no validated bioassay protocols (e.g., WB, IHC, IF, FC) for this small-molecule building block. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility sections for general guidance on cross-couplings and related transformations.

If preparing assay stocks for research screening, typical practice is to dissolve in DMSO (e.g., 10–50 mM), filter if needed, and dilute into the assay medium maintaining final DMSO ≤1–2% v/v; verify solubility and stability in your specific system.

Biological Roles

This product is a synthetic heteroaromatic building block, not a biological reagent. No intrinsic biological role is specified for this item.

General context (literature; for medicinal chemistry background only, not a product claim):

• Cinnoline scaffolds (benzofused 1,2-diazines) occur in numerous research compounds used to probe enzyme active sites and metal-binding pockets due to the diazine nitrogens’ ability to accept hydrogen bonds and coordinate metals.
• Substitution at the 5-position modulates the electron density and pKa of ring nitrogens, influencing target engagement profiles in discovery programs. The bromo group serves as a handle to introduce diverse substituents for SAR.
• Physicochemical characteristics typical of cinnolines include planarity, aromaticity, and modest basicity; these features can affect permeability and binding mode when incorporated into larger research molecules.

Important: Aladdin Scientific supplies 5-bromocinnoline strictly for research and laboratory use. No medical, diagnostic, or clinical applications are intended or supported.

Buffer Applications

Not typically applicable. 5-Bromocinnoline is a neutral heteroaromatic building block rather than a buffering agent. It does not constitute a defined acid/base conjugate pair with an appropriate pKa window for preparing laboratory buffers.

Practical note: If stocks are needed for biological assays, dissolve in DMSO or DMF to make concentrated solutions, then dilute into assay media as appropriate, keeping final organic content low to avoid perturbing buffer capacity.

Green Alternatives

Opportunities to improve sustainability when working with 5-bromocinnoline (general/literature):

• Solvent substitution:

  • Replace DMF/NMP/DMAc with greener ethers or esters when feasible.
  • 2-MeTHF or CPME often support Pd-catalyzed couplings with comparable yields and easier workup; toluene or anisole can work for higher-temperature reactions with strong bases.
  • Aqueous micellar media (e.g., TPGS-750-M or MC-1) can enable Suzuki couplings at lower catalyst loadings; evaluate substrate solubility.

• Base and reagent choices:

  • Use carbonate or phosphate bases in water-containing media to reduce inorganic waste complexity compared to strong alkoxides where possible.
  • Employ boronic esters over organostannanes to avoid toxic tin waste (choose Suzuki over Stille where practical).

• Energy efficiency:

  • Microwaves or continuous flow can shorten reaction times and reduce energy use.
  • Lower-boiling greener solvents (e.g., 2-MeTHF) minimize distillation energy versus high-bp polar aprotics.

• Catalyst economy:

  • Modern ligand systems (SPhos/XPhos/BrettPhos) enable ppm-level Pd loadings; heterogeneous Pd/C or Pd on green supports may be applicable in some couplings.

Comparison snapshot (general):

• Conventional: DMF, 100–140 C; higher E-factor, difficult solvent removal.
• Greener: 2-MeTHF or dioxane/H2O, 60–100 C; simpler workup, lower toxicity.

Note: Validate greener substitutions on small scale; heteroaromatic nitrogens can alter catalyst speciation and require condition optimization.

Pharmaceutical Uses

No pharmacopeial or excipient status is specified for this item; refer to CoA/Spec Sheet.

General context (non-clinical, research/manufacturing perspective only):

• 5-Bromocinnoline is used as a synthetic intermediate in medicinal chemistry and process development to access 5-substituted cinnoline derivatives. The aryl bromide enables late-stage diversification by cross-coupling, allowing efficient parallel synthesis for SAR.
• In preclinical research, heteroaryl bromides like this may be used to prepare reference standards and impurity markers. Any use in GMP or regulated settings would require full qualification of identity, purity, residual solvents, and elemental impurities per ICH guidance—none of which are specified here.
• Formulation/excipient roles: none; this compound is not intended as an excipient or additive.

Compliance notice: For research use only. Not for human or veterinary use, drug substance manufacture, or clinical applications without further qualification and regulatory review.

Physical Properties

Item-specific specs (this batch):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Purity/grade: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general properties for 5-bromocinnoline (for planning only; not product specifications):

• Empirical formula: C8H5BrN2 (literature)
• Formula weight: ~209.04 g/mol (literature, calculated from atomic weights)
• Physical state: typically a crystalline solid (heteroaryl bromides of this mass are commonly solids)
• Solubility profile (qualitative, literature/experience):
  • Poorly soluble in water.
  • Soluble in polar aprotic organic solvents (DMF, DMSO, NMP) and moderately soluble in chlorinated solvents (DCM, CHCl3) and ethers (THF, dioxane); solubility often increases on warming.
• Acidity/basicity: weakly basic ring nitrogens; no strongly ionizable functionality under neutral conditions.
• UV absorption: aromatic chromophore expected to absorb in near-UV (exact λmax not tabulated here).
• Melting point, boiling point, density, logP, refractive index: Not widely tabulated for this specific isomer; consult primary literature or measure as needed for method development.

Notes for method development:

• For LC, reverse-phase methods often require high-organic eluents; addition of small amounts of acid or base can adjust peak shape due to heteroaromatic basicity.
• For NMR, DMSO-d6 or CDCl3 generally provide good solubility; slight warming may help dissolution.

Quality and Grades

Item-specific grade/purity information:

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on grades (general information to help selection; not specific to this lot):

• Research-grade heteroaryl building blocks are typically offered at assay ≥95% by HPLC/GC/NMR unless otherwise stated. Higher grades (≥98%) may be preferred for catalyst screening or sensitive medicinal chemistry SAR studies to minimize side-product background.
• Residual metal content, halide content, and related-structure impurities are critical for cross-coupling performance and analytical clarity but are not specified here. If your application is catalysis-sensitive or for GLP studies, request the CoA with impurity profile and residual solvents.
• Stabilizers: none are typically added to aryl bromides like 5-bromocinnoline; if a stabilizer were used, it would be declared in the CoA. Presence of stabilizers can affect analytical baselines and should be considered for LC-UV or MS.
• Lot-specific tests you may request/verify on the CoA:
  • Identity by 1H NMR/13C NMR and HRMS
  • Assay/purity by HPLC
  • Water content by Karl Fischer (if relevant to your process)
  • Residual solvents (GC) and inorganic residues (ash)

Note: Always rely on the CoA/Spec Sheet for item-specific specifications and test methods.

Reaction and Applications

As a brominated diazine-fused aromatic, 5-bromocinnoline is a versatile electrophile and heteroaryl scaffold. Typical research applications (literature/general):

• Cross-coupling electrophile:
  • Suzuki–Miyaura coupling with aryl/alkenyl boron reagents to access 5-substituted cinnolines. Pd(PPh3)4, Pd(dppf)Cl2, or XPhos-type catalysts with K2CO3, K3PO4, or Cs2CO3 are commonly effective.
  • Stille and Negishi couplings for sensitive partners where boronates underperform.
  • Sonogashira coupling to install alkynyl substituents (Pd/Cu co-catalysis or copper-free variants).
• Buchwald–Hartwig amination: Formation of C–N bonds at C-5 using Pd2(dba)3 or Pd(OAc)2 with biaryl phosphines (e.g., BrettPhos, XPhos) and strong bases (NaOtBu). Note that the diazine nitrogens can coordinate Pd; ligand choice and base strength are important to maintain catalyst activity.
• Direct functionalization strategies: Lithiation or metal–halogen exchange at C-5 (e.g., with n-BuLi or i-PrMgCl·LiCl) followed by electrophile quench can introduce formyl, acyl, or other groups; low temperatures and careful quench are advised due to heteroaryl sensitivity.
• N-oxide chemistry: Temporary oxidation to the N-oxide can direct C–H functionalization elsewhere on the scaffold (then deoxygenation), enabling regiocontrol in multi-step synthesis.
• Scaffold use in discovery chemistry: The cinnoline core provides dual ring nitrogens for H-bonding/coordination; substitution at C-5 modulates electronics and heteroatom basicity for SAR exploration.

Practical tips:

• Rigorous exclusion of air/moisture improves cross-coupling reproducibility.
• Pre-activate sluggish boron partners (e.g., use boronic acids pinacol esters or MIDA boronates) and optimize base/solvent to counter ligand sequestration by ring nitrogens.

Reaction Conditions

Representative literature-style conditions for 5-bromocinnoline (guidance only; optimize per substrate):

• Suzuki–Miyaura coupling:

  • Catalyst: Pd(dppf)Cl2·DCM (1–3 mol%) or Pd(PPh3)4 (2–5 mol%).
  • Base: K2CO3 or K3PO4 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (4:1) or 2-MeTHF/H2O.
  • Temperature/time: 70–100 C, 2–12 h.
  • Notes: Use boronic esters to improve stability; biaryl phosphine ligands (SPhos/XPhos) help with heteroaryl substrates.

• Sonogashira coupling:

  • Catalyst: PdCl2(PPh3)2 (1–2 mol%) with CuI (5–10 mol%) or copper-free with Pd and bulky phosphines.
  • Base: Et3N, i-Pr2NH, or K2CO3.
  • Solvent: THF, MeCN, or 2-MeTHF.
  • Temperature/time: rt–80 C, 2–16 h.

• Buchwald–Hartwig amination:

  • Catalyst: Pd2(dba)3 (1–2 mol% Pd) with BrettPhos or XPhos (2–4 mol%).
  • Base: NaOtBu or Cs2CO3 (2–3 equiv).
  • Solvent: toluene, dioxane, or CPME.
  • Temperature/time: 80–110 C, 4–18 h.
  • Tip: Increase ligand:Pd ratio to mitigate binding by diazine nitrogens.

• Metal–halogen exchange/electrophile trap:

  • Reagent: i-PrMgCl·LiCl (2–3 equiv) or n-BuLi (1.1–1.5 equiv) at −78 to −20 C in THF or Et2O.
  • Quench: DMF (for formylation), CO2 (acid), or electrophiles (R–X, acyl chlorides).

Yield expectations: With optimized conditions, 60–90% isolated yields are typical for cross-couplings on heteroaryl bromides (literature). Always monitor by TLC/LC–MS and adjust ligand/base/solvent for best performance.

Safety and Handling

Item-specific safety details:

• GHS classification, pictograms, signal word, and H-statements: Not specified for this item; refer to SDS.

General safety considerations for heteroaryl bromides (literature/good practice; defer to SDS for authoritative guidance):

• Likely hazards: May cause skin/eye irritation or respiratory irritation upon dust inhalation. Avoid dust generation and inhalation.
• Personal protective equipment (PPE):
  • Lab coat, nitrile gloves, safety glasses/goggles.
  • Handle powders in a fume hood to control dust and vapors from solvents used in processing.
• Handling/storage incompatibilities:
  • Avoid strong oxidizers and strong bases/acids during storage. In reactions, bases are commonly used but should be handled with appropriate controls.
  • As an aryl bromide, not prone to peroxide formation; no special peroxide precautions are necessary for the solid itself.
• First aid (overview):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: Wash with soap and water; remove contaminated clothing.
  • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; seek medical advice if irritation continues.
  • Ingestion: Rinse mouth; seek medical attention.
• Fire safety: Organic solid; combustible. Use CO2, dry chemical, or foam for fires. Thermal decomposition may release hydrogen bromide and nitrogen oxides.
• Waste: Collect organic solid waste and contaminated solvents in appropriate hazardous waste streams per institutional and local regulations.

Solvent Selection

Solubility and solvent behavior (general/literature for 5-bromocinnoline):

• Polarity class: moderately polar aromatic heterocycle; largely non-ionic under neutral conditions.
• Water: poorly soluble.
• Good solvents: DMSO, DMF, NMP, dioxane, THF, acetone, acetonitrile; moderate in chlorinated solvents (DCM, CHCl3). Solubility improves with temperature.
• Protic solvents: lower solubility than in polar aprotics; MeOH/EtOH may be serviceable for workups or recrystallization mixtures.

Selection guidance by use-case:

• Cross-coupling (Suzuki/Stille/Buchwald/Sonogashira): dioxane/H2O, toluene, THF, CPME, or Me-THF are common. Polar aprotics (DMF, DMAc, NMP) enable higher temperatures for difficult couplings but can complicate workup.
• Nucleophilic substitutions or lithiation strategies: ethers (THF, TBME) or hydrocarbons (toluene) under strong base; ensure dryness.
• Analytical prep (HPLC): Reverse-phase methods typically use MeCN/H2O or MeOH/H2O; add 0.1% formic acid or ammonium formate for MS compatibility and peak shape.

Quick comparison (general):

• Dioxane/H2O: balances solubility and base compatibility; common in Suzuki.
• 2-MeTHF/CPME: greener ethers; good for Pd-catalyzed couplings, easier workup than DMF.
• DMF/NMP: dissolve substrates well; higher bp for elevated temps; harder to remove and less green.

Note: Verify actual solubility with a small-scale test in your chosen solvent system.

Storage and Reconstitution

Item-specific storage conditions:

• Storage Conditions: Room temperature (per Product Data).
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General handling guidance:

• Keep container tightly closed in a dry, well-ventilated place. Protect from excessive heat and direct sunlight. Store under inert atmosphere if long-term storage is planned to minimize potential oxidative discoloration.
• Hygroscopicity: Not known to be strongly hygroscopic; nevertheless, minimize moisture ingress to preserve assay and facilitate accurate weighing.

Reconstitution/stock solutions (research use):

• This is a solid; no reconstitution is required for storage. For working solutions, dissolve in dry organic solvents such as DMSO, DMF, THF, dioxane, or acetonitrile. Filter through a PTFE membrane if particulate persists.
• Typical screening stocks: 10–50 mM in DMSO; store aliquots at −20 C to avoid repeated freeze–thaw and moisture uptake. Allow to equilibrate to room temperature before opening to prevent condensation.
• Stability in solution: Evaluate by LC–MS/HPLC over time; heteroaryl bromides are generally stable in anhydrous aprotic media but may slowly hydrolyze or debrominate under strongly basic or photolytic conditions.

Note: For definitive shelf-life, impurity limits, and solution stability, consult the lot-specific CoA/SDS and perform application-specific verification.

Structure and Identity

Brief overview: 5-Bromocinnoline is a halogenated diaza-fused benzene (cinnoline) bearing a bromine substituent at the 5-position, useful as a heteroaryl coupling partner and scaffold.

• Item-specific identifiers from Product Data:

  • CAS: 1823964-40-4
  • SKU: B944754
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (catalog field shows a placeholder)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identifiers (for reference; not item specifications):

  • Preferred IUPAC name (literature): 5-bromocinnoline
  • Molecular formula (literature): C8H5BrN2
  • Molecular weight (literature): ~209.04 g/mol
  • Structural class: bicyclic aromatic diazine (benzopyridazine)

• Structural description (2D, literature):

  • A benzene ring fused to a 1,2-diazine (pyridazine) ring (the cinnoline core), with ring nitrogens at positions 1 and 2 of the diazine. A bromine substituent is located at C-5 (on the benzene portion).
  • Functional groups: aromatic C–Br (aryl bromide), two ring nitrogens (diazine), fully conjugated aromatic system.
  • Stereochemistry: none (planar aromatic polycycle).

Synthetic Utility

Key functional elements and reactivity (literature/general):

• Electrophilic site: aryl C–Br at C-5 enables Pd-, Ni-, or Cu-catalyzed cross-couplings (Suzuki, Stille, Negishi, Kumada, Sonogashira) to introduce aryl, alkenyl, alkynyl, or alkyl substituents.
• Heteroaryl effects: The adjacent diazine nitrogens modulate oxidative addition kinetics and can coordinate metal catalysts. Bulky, electron-rich ligands (e.g., XPhos, SPhos, BrettPhos) often enhance reactivity and suppress catalyst deactivation.
• Orthogonal strategies:
  • Metal–halogen exchange (e.g., with i-PrMgCl·LiCl or n-BuLi at low temperature) grants access to 5-metallated cinnoline intermediates for electrophile trapping (formylations, acylations, halogenations).
  • Directed lithiation or electrophilic aromatic substitution elsewhere on the ring can be orchestrated via temporary protection/activation (e.g., N-oxide formation) for regiocontrol.
• Late-stage diversification: The stable aryl bromide tolerates many functional groups, facilitating convergent syntheses of cinnoline-containing targets.

Practical synthesis notes:

• Maintain anhydrous, oxygen-free conditions for organometallics and cross-couplings.
• Consider pre-catalyst forms (e.g., Pd-precatalysts with biaryl phosphines) to ensure rapid activation in the presence of coordinating nitrogens.
• For challenging substrates, switch to Ni catalysis or employ additive strategies (e.g., KF, TBAB) to enhance transmetalation.

Utility summary: 5-Bromocinnoline is a modular entry point to a broad chemical space of cinnoline derivatives, enabling efficient SAR and scaffold elaboration.

Target Specificity

Not applicable. 5-Bromocinnoline is a small-molecule chemical building block and does not have an inherent biological target or antigen specificity. No antibody/biomolecule attributes (epitope, clone, isotype, species reactivity) apply.